Methods and systems for removal of a targeted tissue from the body

ABSTRACT

Methods and systems for acoustic treatment of tissue are provided. Acoustic energy, for example ultrasound energy, under proper functional control can penetrate deeply and be controlled precisely in tissue. Some aspects provide a method configured for removal of at least a portion of targeted tissue, such as a scar, abscess, non-cancerous tumor, or fibrous knot, in a tissue of the body.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.15/001,712, filed Jan. 20, 2016, which is based on, claims priority to,and incorporates herein by reference U.S. Provisional Patent ApplicationSer. No. 62/105,512, filed Jan. 20, 2015.

BACKGROUND

Current methods for the removal of a targeted tissue from the skin or atissue in a patient are varied and have mixed results. A targeted tissueembedded in the skin may be cut out, but will often be painful and leavea scar. Ultrasound methods have attempted to use shock waves, but theyare limited to certain types of targeted tissues and damage thesurrounding tissue. Likewise the technique of ablation is limited toonly certain types of target tissues. Accordingly, it would be useful todevelop new techniques for removing a targeted tissue in a tissue of thebody of a patient with fewer side-effects and limitations of specifictechnologies to specific tissues.

SUMMARY

The present disclosure overcomes the aforementioned drawbacks bypresenting a method for removal of targeted tissue from the body whichutilizes acoustic energy treatment.

This disclosure provides a method for acoustic treatment of tissues forremoval of targeted tissue which can be non-invasive. The method caninclude directing acoustic energy deposition into a tissue by creatingan energy distribution function. The energy distribution function can betuned to control treatment of a target zone within a tissue, targetedtissue embedded in the tissue, or any combination thereof to remove atargeted tissue or portion thereof. Examples of a targeted tissue are,but are not limited to, a hypertrophic scar, a keloidal scar, anabscess, a cancerous or non-cancerous tumor, a fibrous knot, orcombinations thereof, in a body.

In one aspect, this disclosure provides a method of removing targetedtissue by inducing an acousto-mechanical or acousto-elastic effect inthe targeted tissue embedded in a medium. The method can include one ormore of the following steps: coupling an ultrasound energy source to thetargeted tissue; and directing a pulsed first ultrasound energy from theultrasound energy source into the targeted tissue, thereby initiating anacousto-mechanical or acousto-elastic effect in the targeted tissue. Theultrasound energy source can be configured to produce a pulsed firstultrasound energy having a frequency of between 100 kHz and 200 MHz anda pulse duration of between 1 ps and 1 ms. The ultrasound energy sourcecan be configured to produce a pulsed first ultrasound energy having afrequency of between 100 kHz and 200 MHz, a pulse duration of between 1ps and 1 ms, and a power of between 1 kW and 50 kW. The pulsed firstultrasound energy can have a pulse energy from 500 nJ to 5 J. Theacousto-mechanical or acousto-elastic effect in the targeted tissue canexceed a fragmentation threshold of the targeted tissue.

In another aspect, this disclosure provides a method of removing atargeted tissue by treating the targeted tissue or a portion thereof ina body. The method can include one or more of the following steps:coupling an ultrasound energy source to the targeted tissue embedded ina tissue; and initiating, using a single ultrasound energy pulse fromthe ultrasound energy source, an acousto-mechanical or acousto-elasticeffect in the targeted tissue that exceeds a fragmentation threshold ofthe targeted tissue and can fragment the targeted tissue or a portionthereof into a plurality of sub-particles of a size that can initiate animmune response which can remove the sub-particles, thereby removing thetargeted tissue or a portion thereof.

In yet another aspect, this disclosure provides an ultrasound treatmentsystem for removal of a targeted tissue, a portion thereof, orsub-particles thereof in a body. The ultrasound treatment system caninclude an ultrasound source and a control system. The ultrasound sourcecan be configured to emit a propagating ultrasound energy having apropagating ultrasound pulse duration between 100 ps and 1 ms, apropagating ultrasound pulse power ranging from 1 kW to 50 kW, and apropagating ultrasound frequency between 100 kHz and 200 MHz. Thecontrol system can be configured to direct the ultrasound energy sourceto emit the propagating ultrasound energy to a target zone within thetissue containing a targeted tissue at an intensity gain between 500 and25,000, thereby initiating an acousto-mechanical or acousto-elasticeffect within the target zone. The acousto-mechanical or acousto-elasticeffect can move the targeted tissue, a portion thereof, or sub-particlesthereof. The targeted tissue, a portion thereof, or sub-particlesthereof can be moved toward the surface of the tissue, expelling themfrom the tissue, or moved deeper into the tissue, to be absorbed by thebody or removed by the immune system.

BRIEF DESCRIPTIONS OF THE DRAWINGS

FIG. 1 is a cross-sectional view of layers of tissues, illustrating theplacement of a targeted tissue.

FIG. 2 is a block diagram illustrating an exemplary ultrasound deliverysystem, according to one aspect of the present disclosure.

FIG. 3 is a block diagram of an exemplary ultrasound source, accordingto one aspect of the disclosure.

FIG. 4A is a cross-sectional view illustrating one stage of exemplarymethod, according to one aspect of the present disclosure.

FIG. 4B is a cross-sectional view illustrating one stage of exemplarymethod, according to one aspect of the present disclosure.

FIG. 4C is a cross-sectional view illustrating one stage of exemplarymethod, according to one aspect of the present disclosure.

FIG. 5 is a graphical representation of the relationship between energyeffects and acoustic pulse duration, according to one aspect of thepresent disclosure.

FIG. 6 is a flow chart of an exemplary method, according to one aspectof the present disclosure.

DETAILED DESCRIPTION

Before the present invention is described in further detail, it is to beunderstood that the invention is not limited to the particularembodiments described. It is also understood that the terminology usedherein is for the purpose of describing particular embodiments only, andis not intended to be limiting. The scope of the present invention willbe limited only by the claims. As used herein, the singular forms “a”,“an”, and “the” include plural embodiments unless the context clearlydictates otherwise.

Specific structures, devices and methods relating to ultrasoundtreatment and operation for the removal of a targeted tissue from atissue of the body are disclosed. It should be apparent to those skilledin the art that many additional modifications beside those alreadydescribed are possible without departing from the inventive concepts. Ininterpreting this disclosure, all terms should be interpreted in thebroadest possible manner consistent with the context. Variations of theterm “comprising” should be interpreted as referring to elements,components, or steps in a non-exclusive manner, so the referencedelements, components, or steps may be combined with other elements,components, or steps that are not expressly referenced. Embodimentsreferenced as “comprising” certain elements are also contemplated as“consisting essentially of” and “consisting of” those elements. When twoor more ranges for a particular value are recited, this disclosurecontemplates all combinations of the upper and lower bounds of thoseranges that are not explicitly recited. For example, recitation of avalue of between 1 and 10 or between 2 and 9 also contemplates a valueof between 1 and 9 or between 2 and 10.

The various embodiments may be described herein in terms of variousfunctional components and processing steps. It should be appreciatedthat such components and steps may be realized by any number of hardwarecomponents configured to perform the specified functions. For example,various embodiments may employ various cosmetic enhancement devices,visual imaging and display devices, input terminals and the like, whichmay carry out a variety of functions under the control of one or morecontrol systems or other control devices. In addition, the embodimentsmay be practiced in any number of medical, non-medical, or cosmeticcontexts and the various embodiments relating to a method and system foracoustic tissue treatment for removal of a targeted tissue from a tissueas described herein are merely indicative of some examples of theapplication for use in medical treatment or cosmetic enhancement. Forexample, the principles, features, and methods discussed may be appliedto any medical, non-medical, or cosmetic application. Further, variousaspects of the various embodiments may be suitably applied to medical,non-medical, or cosmetic applications for the skin, subcutaneous layers,or combinations thereof.

As used herein, the term “cosmetic enhancement” can refer to procedures,which are not medically necessary and are used to improve or change theappearance of a portion of the body. Since it is not medically indicatedfor improving one's physical well-being, cosmetic enhancement does notdiagnose, prevent, treat, or cure a disease or other medical condition.Furthermore, cosmetic enhancement is not a method for treatment of thehuman or animal body by surgery or therapy nor a diagnostic methodpracticed on the human or animal body. Cosmetic enhancement is anon-surgical and non-invasive procedure. In some aspects, cosmeticenhancement can be a non-surgical and non-invasive procedure that isperformed at home by a user who is not a medical professional.

As used herein, the term “lesion” shall refer to a void, a lesion, or acombination thereof, unless the context clearly dictates otherwise.

As used herein, the term “targeted tissue” shall refer to, but is notlimited to, a hypertrophic scar, a keloidal scar, an abscess, anon-cancerous tumor, cancerous lesions, conglomeration of melanin, afibrous knot, or combinations thereof, in a body or tissue. Otherexamples of the targeted tissue can include, but are limited to, scartissue, melanocyte or melanin (hyperpigmentation), sebaceous gland,hair, a piece of cartilage, a tumor (either cancerous or benign), a fatcell, a muscle, and combinations thereof.

As used herein, the term “tissue” may refer to, but is not limited to,at least one of an epidermal layer, a dermal layer, a fat layer, amuscle layer, a subcutaneous tissue, or combinations thereof, in a body.

As used herein, the term “fragmentation” shall refer to any pressure- ortemperature-induced expansion within a material that breaks apart thematerial, including a micro-explosion, a fragmentation, or a combinationthereof, unless the context clearly dictates otherwise.

As used herein, the term “fragmentation threshold” shall refer to theminimum amount of energy directed at an object in a region of interestwhich causes the object to fragment. Fragmentation can be the result ofan acousto-mechanical effect which rapidly increases pressure, anacousto-elastic effect which rapidly increases temperature, or acombination thereof.

This disclosure provides systems and methods for removal of a targetedtissue from a body or tissue which utilizes acoustic energy treatment oftissue.

Referring to FIG. 1, a cross-sectional view of layers of tissue in abody, illustrating a schematic of an embedded targeted tissue. Atargeted tissue 90 of a size which cannot be up-taken by immune cells ortransported to lymphatic channels 92 for clearance, are present in atissue 80.

Referring to FIG. 2, this disclosure provides an ultrasound deliverysystem 100. The ultrasound delivery system can include an ultrasoundenergy source 102 and a control system 104, which can be electronicallycoupled to one another via one or more communication conduits 106. Theone or more communication conduits 106 can be wired or wireless. Theultrasound energy source 102 can be configured to emit propagatingultrasound energy 108. The control system 104 can be configured todirect the ultrasound energy source 102 to emit propagating ultrasoundenergy 108.

Still referring to FIG. 2, this disclosure provides systems and methodswhere the ultrasound energy source 102 can transmit ultrasound energy108 across an optional boundary 110, such as a surface, and into aregion of interest (“ROI”) 112. The propagating ultrasound energy 108can be delivered to a target zone 114 within the ROI 112 containing atleast part of a targeted tissue 90. The propagating ultrasound energy108 can create an acoustic energy field 116 within the ROI 112. The ROI112 can include a medium, as described herein.

In certain aspects, the ultrasound energy source 102 can be positionedwithin an ultrasound probe. The ultrasound probe can optionally behandheld. The control system 104 can be located within the ultrasoundprobe or remote from the ultrasound probe.

Referring to FIG. 3, the ultrasound energy source 102 can include atransducer 118, which is configured to emit propagating ultrasoundenergy 108. The ultrasound energy source can further include a functiongenerator 120, which can be powered by a power supply 122. The functiongenerator 120 can be a radiofrequency (“RF”) generator, a frequencygenerator, a pulse generator, a waveform generator, or a combinationthereof. The power supply 122 can be located within the ultrasoundenergy source 102 or remote from the ultrasound energy source 102. Thefunction generator can provide a drive signal to the transducer 118 thatinitiates the emission of propagating ultrasound energy 108. The drivesignal can have a drive frequency and a drive amplitude. The drivesignal can be an RF signal. The ultrasound energy source 102 canoptionally include an amplifier 124 that is configured to receive thedrive signal, controllably amplify the drive signal to produce anamplified drive signal, and transmit the amplified drive signal to thetransducer 118. The ultrasound energy source 102 can further optionallyinclude an impedance matching network 126. The impedance matchingnetwork 126 can be configured to adjust the effective impedance or theload of the transducer 118 to match the impedance of the functiongenerator 120 or the amplifier 124. The impedance matching network 126can be configured to receive the drive signal from the functiongenerator 120 and transmit a matched drive signal to the transducer 118or to receive the amplified drive signal from the amplifier 124 andtransmit a matched, amplified drive signal to the transducer 118.

In certain aspects, the propagating ultrasound energy 108 can be pulsed.The propagating ultrasound energy 108 can have a propagating ultrasoundpulse duration ranging from 100 ps to 1 ms, including but not limitedto, a propagating ultrasound pulse duration ranging from 100 ps to 1 μs,from 100 ps to 100 μs, from 500 ps to 500 ns, from 500 ps to 750 ns,from 1 ns to 10 μs, from 1 ns to 500 μs, from 200 ns to 1 ms, from 500ns to 500 μs, from 1 us to 50 μs, from 1 us to 1 ms, or combinations ofthe lower and upper bounds of those ranges which are not explicitly setforth. The propagating ultrasound energy 108 can have a propagatingultrasound pulse power ranging from 1 kW to 50 kW, including but notlimited to, a propagating ultrasound pulse power ranging from 1 kW to 5kW, or from 1 kW to 10 kW. The propagating ultrasound energy 108 canhave a propagating ultrasound pulse energy ranging from 500 nJ to 5 J,including but not limited to, a propagating ultrasound pulse energyranging from 500 nJ to 2.5 mJ, from 500 nJ to 37.5 mJ, from 500 nJ to100 mJ, from 500 nJ to 500 mJ, from 2000 to 5 J, from 500 μJ to 5 J,from 1 mJ to 250 mJ, from 1 mJ to 5 J, or combinations of the lower andupper bounds of those ranges which are not explicitly set forth.Ultrasound pulse durations described herein correspond to the durationof the ultrasound pulse itself and not the duration of a drive pulse orany other pulses related to the generation of ultrasound. Ultrasoundpulse durations can be measured as a −6 dB pulse beam-width or a −3 dBpulse beam width.

In certain aspects, the propagating ultrasound energy 108 can have aspecific frequency. The propagating ultrasound energy 108 can have apropagating ultrasound frequency ranging from 100 kHz to 200 MHz,including but not limited to, a propagating ultrasound frequency rangingfrom 500 kHz to 25 MHz, from 500 kHz to 200 MHz, from 1 MHz to 5 MHz,from 1 MHz to 7 MHz, from 1 MHz to 10 MHz, from 1 MHz to 20 MHz, from 1MHz to 25 MHz, from 1 MHz to 30 MHz, from 1 MHz to 50 MHz, from 1 MHz to200 MHz, from 2 MHz to 5 MHz, from 2 MHz to 10 MHz, from 2 MHz to 200MHz, from 3 MHz to 7 MHz, or combinations of the lower and upper boundsof those ranges which are not explicitly set forth.

In certain aspects, the ultrasound energy source 102 can be configuredto deliver propagating ultrasound energy 108 to the target zone 116 withan intensity gain relative to the intensity immediately after emissionfrom the ultrasound energy source 102. The intensity gain can be in arange from 500 to 25,000, including but not limited to, a range from1000 to 10,000. The intensity gain can be at least 500 or at least 1000.

In certain aspects, the ultrasound energy 108 can be configured to bedelivered to various depths below a surface. For example, the ultrasoundenergy 108 can be configured to be delivered to a depth between 0.1 mmand 50 mm below a surface, including but not limited to, a depth between0.2 mm and 2 mm, or a depth of at least 3 mm below the surface.

In certain aspects, the ultrasound delivery system 100 can furtherinclude an ultrasound imager configured to image at least a portion ofthe ROI 112. The ultrasound imager can be located within the ultrasoundprobe or remote from the ultrasound probe. The ultrasound imager can beused, but is not limited to, in determining the depth or size of atargeted tissue 90 within the tissue 80.

In certain aspects, the ultrasound delivery system 100 can furtherinclude a secondary ultrasound energy source configured to delivery asecondary propagating ultrasound energy to the ROI 112 or the targetedtissue 90 thereby establishing a secondary ultrasound energy fieldtherein. A set of parameters for delivering the secondary ultrasoundenergy can include a secondary ultrasound frequency ranging from 100 kHzto 200 MHz, a secondary ultrasound power ranging from 1 kW to 10 kW, anda secondary ultrasound pulse duration ranging from 500 us to 10 s.Delivering secondary ultrasound energy under these conditions caninitiate a thermal effect, a cavitation effect, or a combination thereofin the targeted tissue 90. For certain applications, the secondaryultrasound frequency can range from about 500 kHz to 25 MHz, from 500kHz to 200 MHz, from 1 MHz to 5 MHz, from 1 MHz to 7 MHz, from 1 MHz to10 MHz, from 1 MHz to 20 MHz, from 1 MHz to 25 MHz, from 1 MHz to 30MHz, from 1 MHz to 200 MHz, from 2 MHz to 5 MHz, from 2 MHz to 10 MHz,from 2 MHz to 200 MHz, or combinations of the lower and upper bounds ofthose ranges which are not explicitly set forth. For certainapplications, the secondary ultrasound power can range from 1 kW to 10kW. For certain applications, the secondary pulse duration can rangefrom 500 us to 1 ms, from 500 us to 10 ms, from 500 us to 100 ms, from500 us to 1 s, from 1 ms to 50 ms, from 1 ms to 500 ms, from 1 ms to 1s, from 1 ms to 10 s, from 50 ms to 100 ms, from 50 ms to 1 s, from 50ms to 10 s, from 100 ms to 1 s, from 500 ms to 10 s, or from 1 s to 10s, or combinations of the lower and upper bounds of those ranges whichare not explicitly set forth.

In certain aspects, the ultrasound delivery system 100 can furtherinclude a secondary energy source configured to delivery a secondaryenergy to at least a portion of the ROI 112. The secondary energy sourcecan be a photon-based energy source, an RF energy source, a microwaveenergy source, a plasma source, a magnetic resonance source, or amechanical device capable of generating positive or negative pressures.Examples of a photon-based energy source include, but are not limitedto, a laser, an intense pulsed light source, a light emitting diode, andthe like. The secondary energy source can be located within theultrasound probe or remote from the ultrasound probe. The secondaryenergy source can be configured to deliver the secondary energy before,during, or after the delivery of the propagating ultrasound energy 108.In certain aspects, the ultrasound delivery system 100 can furtherinclude an energy sink configured to remove energy from the ROI 112, forexample, by providing a cooling effect the ROI 112.

Referring to FIGS. 4A, 4B, and 4C, a series of cross-sectional views areshown of an ultrasound energy source 102 directing propagationultrasound energy 108 through a first medium layer surface 136, such asa skin surface 98, and a first medium layer 138, such as an epidermislayer 96, into a second medium layer 140, such as a dermis layer 94, butnot into a third medium layer 142, such as a subcutaneous tissue layer,and the resulting effect. The propagating ultrasound energy 108 can bedelivered into a targeted tissue 90 embedded in the first 138, second140, or third medium layer 142.

Referring to FIG. 4A, the cross-sectional view is shown before anacoustic energy field 116 has been established within the targetedtissue 90 and surrounding portion of the second medium layer 140. Aboundary 110, such as the outer surface of the targeted tissue, canseparate the targeted tissue 90 from the second medium layer.

Referring to FIG. 4B, the cross sectional view is shown as thepropagating ultrasound energy 108 passes through the boundary 110 andinto the targeted tissue 90 to produce an acoustic energy field 116 inthe targeted tissue 90 and surrounding portion of the second mediumlayer 140, which can generate a non-linear effect within the targetedtissue 90. In certain aspects, the non-linear effect can be anacousto-mechanical effect, an acousto-elastic effect, or a combinationthereof in the targeted tissue 90.

Referring to FIG. 4C, the cross-sectional view is shown after thenon-linear effect has caused a fragmentation in the targeted tissue 90,which can create a plurality of sub-particles 146. In certain aspects,the sub-particles 146 are of a size which renders them less visible thanthe targeted tissue 90 from the surface. In certain aspects, thesub-particles 146 are of a size which can be up-taken by immune cellsand transported to the lymph system through lymphatic channels 92 forclearance. In certain aspects, an acoustic impedance of the targetedtissue 90 can be greater than an acoustic impedance of the second mediumlayer 140 and the boundary 110 can be the site of an acoustic impedancemismatch between the targeted tissue 90 and the second medium layer 140.

The targeted tissue 90 can have a diameter of between 10 nm and 500 μm,including but not limited to, a diameter of between 25 nm and 250 μm,between 50 nm and 100 μm, between 100 nm and 50 μm, between 250 nm and10 μm, between 500 nm and 1 μm, or combinations of the lower and upperbounds of those ranged which are not explicitly set forth.

Referring to FIG. 5, a graphical representation 200, which has an x-axis201 of ultrasound pulse duration represented as time and a y-axis 211 ofultrasound pulse intensity, illustrates the domains of variousultrasound sound energy initiated effects in a medium. Also asillustrated, some of the domains can overlap. These domains areapproximations and the boundaries of the domain may shift for variousreasons, such as changes in frequency, differences in the medium, orboth. A person having ordinary skill in the art can calculate theeffects of these changes using the equations described herein andequations known to those having ordinary skill in the art. These domainscan be approximations in a frequency range of 1 MHz to 2 GHz. However,the frequency range can be narrower, for example, from 1 MHz to 30 MHz.In some applications, the frequency range can be from 1 MHz to 10 MHz,from 1 MHz to 7 MHz, or from 2 MHz to 5 MHz.

Still referring to FIG. 5, the first domain to be discussed is thedomain of a thermal effect 208. The thermal effect raises thetemperature of the medium by creating friction of molecules in thetarget zone of the medium from the oscillations of the acoustic energy.Different energy distribution fields can create one or more thermaleffects in the medium. The energy distribution field can create aconformal elevated temperature distribution in the target zone of themedium. The ultrasound pulse duration for the domain of a thermal effect208 is in a range from ms to minutes in a frequency range, as describedabove.

Still referring to FIG. 5, the second domain to be discussed is thedomain of cavitation 206. At sufficiently high acoustic intensities,cavitation is the formation of microbubbles in a liquid portion of amedium. The interaction of the ultrasound field with the microbubblescan cause the microbubbles to oscillate in the medium (non-inertialcavitation or dynamic cavitation) or to grow and eventually implode(inertial cavitation). During inertial cavitation, very hightemperatures inside the bubbles occur, and the collapse is associatedwith a shock wave that can mechanically damage the medium. However, theresulting damage to the medium is typically unpredictable. Theultrasound energy is unable to cause a cavitation effect in a solidmedium because a truly solid medium does not contain any liquid, whichis required for formation of microbubbles. The ultrasound pulse durationfor the domain of cavitation 206 is in a range from ms to seconds in afrequency range, as described above. There is an overlap 226 of thedomain of a thermal effect 208 and the domain of cavitation 206. In theoverlap 226, both of the effects, the thermal effect and the cavitationeffect can occur.

Still referring to FIG. 5, the third domain to be discussed is thedomain of acousto-mechanical effect 204. The acousto-mechanical effectis a destruction of a target zone in a medium by overcoming theinteraction energy of the molecules in the target zone with theultrasound energy. For example, acousto-mechanical effect can overcome aheat capacity of a medium by mechanical means, which can dramaticallyincrease pressure in the target zone from the inside out, thus resultingin a significant increase of temperature in the target zone. Thepressure, P(r,t), generated at time t and position r by theacousto-mechanical effect can be described by the following equation:

$\begin{matrix}{{{\nabla^{2}{P\left( {r,t} \right)}} - {\frac{1}{v^{2}}\frac{\partial^{2}{P\left( {r,t} \right)}}{\partial t^{2}}}} = {{- \frac{\beta}{C_{p}}}\frac{\partial{h\left( {r,t} \right)}}{\partial t}}} & (1)\end{matrix}$

where β is the thermal expansion coefficient of the medium, v is thespeed of sound in the medium, C_(p) is the heat capacity of the medium,and h(r,t) is the heat generation per unit time and volume within themedium. The acousto-mechanical effect can cause a fragmentation in thetarget zone of the medium. The acousto-mechanical effect can cause anincrease in a pressure in the target zone above a threshold offragmentation of the medium in the target zone. A fragmentation pressureis a minimum pressure at which a substance (for example a targetedtissue) in the target zone of a particular medium (for example a tissuein a body) will explode (shatter, fragment). The ultrasound pulseduration for the domain of an acousto-mechanical effect 204 is in arange from ns to ms in a frequency range, as described above. There isan overlap 224 of the domain of cavitation 206 and the domain of anacousto-mechanical effect 204. In the overlap 224, both the cavitationand the acousto-mechanical effect can occur.

Still referring to FIG. 5, the fourth domain to be discussed is thedomain of acousto-elastic effect 202. The acousto-elastic effect is aneffect in a medium that arises from the combination of the pressureoscillations of an acoustic wave with the accompanying adiabatictemperature oscillations in the medium produced by the acoustic wave.Temperature of the surrounding medium is unchanged. The acousto-elasticeffect is an effect in that can overcome threshold of elasticity of themolecules in the target zone of the medium. The acousto-elastic effectincreases the temperature from the inside out by thermal diffusion,which can dramatically increase temperature in a target zone thusresulting in a raise in pressure in the target zone. The temperature,T(r,t), generated at time t and position r by the acousto-elastic effectcan be described by the following equation:

$\begin{matrix}{{\frac{\partial{T\left( {r,t} \right)}}{\partial t} - {\alpha{\nabla^{2}{T\left( {r,t} \right)}}}} = \frac{h\left( {r,t} \right)}{\rho\; C_{p}}} & (2)\end{matrix}$

where α is the thermal diffusion coefficient of the medium and ρ is thedensity of the medium. The acousto-elastic effect can break the thermalelastic connection of the molecules in the target zone 114, which cancause a fragmentation in the target zone of the medium. Theacousto-elastic effect can raise a temperature in the target zone abovea fragmentation temperature of the medium in the target zone. Afragmentation temperature is a minimum temperature at which a substance(for example a targeted tissue) in the target zone of a particularmedium (for example a tissue or layers of tissue in a body) will explode(shatter, fragment). The ultrasound pulse duration for the domain of anacousto-mechanical effect 202 is in a range from ps to ms in a frequencyrange, as described above. There is an overlap 222 of the domain of anacousto-mechanical effect 204 and the domain of acousto-elastic effect202. In the overlap 222, both of the effects, the acousto-mechanicaleffect and the acousto-elastic effect can occur.

The acousto-mechanical effect causes a massive and rapid increase inpressure in a target zone of the medium. The acousto-elastic effectcauses a massive and rapid increase of temperature in a target zone ofthe medium. The acousto-mechanical effect and the acousto-elastic effectare different than a photo-acoustic effect. A photo-acoustic effect isthe conversion of light energy into acoustic energy. Theacousto-mechanical effect and the acousto-elastic effect are differentthan a photo-mechanical effect. A photo-mechanical effect is theconversion of light energy into mechanical energy. Accordingly, anultrasound source cannot initiate a photo-acoustic or photo-mechanicaleffect. In certain aspects, an acousto-mechanical or acousto-elasticeffect can initiate a change in a state of matter of a material.

Spatial control of the acoustic energy field 116 can be achieved byspatial control of the propagating ultrasound energy 108 emission. Onemeans of achieving spatial control of the propagating ultrasound energy108 emission is through the configuration of the ultrasound energysource 102 by way of the control system 104. For example, spatialcontrol can be achieved through one or more of the following: varyingthe placement of the acoustic energy source 102; varying the orientationof the acoustic energy source 102 in any of six degrees of freedom,including three translational degrees of freedom and three rotationaldegrees of freedom; varying environmental parameters, such as thetemperature of an acoustic coupling interface; varying the couplingagent; varying the geometric configuration of the acoustic energy source102; varying the number of transduction elements or electrodes in theultrasound energy source 102; utilizing one or more lenses, variablefocusing devices, stand-offs, transducer backing, or acoustic matchinglayers; and other spatial control processes known to one having ordinaryskill in the ultrasound arts. Spatial control can be facilitated byopen-loop or closed-loop feedback algorithms, for example, by monitoringa signal or effect and the spatial characteristics that produce thesignal or effect in order to optimize the signal or effect. Thepropagating acoustic energy 108 can be focused to a minimum focal spotsize that is wavelength dependent.

Temporal control of the acoustic energy field 116 can be achieved bytemporal control of the propagating ultrasound energy 108 emission. Onemeans of achieving temporal control of the propagating ultrasound energy108 emission is through the configuration of the ultrasound energysource 102 by way of the control system 104. For example, temporalcontrol can be achieved through one or more of the following: varying adrive amplitude; varying a drive frequency; varying a drive waveform;varying drive timing sequences; varying a pulse repetition rate;apodization of the propagating ultrasound energy 108 emission; othertemporal control processes known to one having ordinary skill in theultrasound arts. Temporal control can be facilitated by open-loop orclosed-loop feedback algorithms, for example, by monitoring a signal oreffect and the temporal characteristics that produce the signal oreffect in order to optimize the signal or effect.

Using the equations and phenomena disclosed herein and other equationsand phenomena known to a person having ordinary skill in the art ofultrasound treatment, a user can determine appropriate spatial andtemporal parameters to provide to the control system 104, which candirect the ultrasound energy source 102 to generate a predictablepropagating ultrasound energy 108 that causes a predictable acousticenergy field 116 within a material, such as a target medium (for examplea tissue or layers of tissue in a body 94) or an object (for example atargeted tissue 90). The acoustic energy field 116 can be described byan acoustic energy function that can be mathematically determined by aperson having ordinary skill in the art by using the equations andphenomena disclosed herein and other equations and phenomena known to aperson having ordinary skill in the art of ultrasound treatment. Theacoustic energy function can include three spatial dimensions and a timedimension.

The acoustic energy field 116 can result from an algebraic, geometric,convolved, or other mathematical combination of two or more acousticenergy fields 116 generated by one or more acoustic energy sources 102.The acoustic energy field 116 can correspond to a designedthree-dimensional thermal energy distribution.

For certain applications, a set of parameters for delivering ultrasoundenergy can include an ultrasound frequency ranging from about 500 kHz toabout 25 MHz, an ultrasound power ranging from about 1 kW to about 10kW, an ultrasound pulse width ranging from about 500 ns to about 500 μs,and an ultrasound energy ranging from about 500 μJ to about 5 J. Forcertain applications, the ultrasound frequency can range from about 1MHz to about 5 MHz. Delivering ultrasound energy under these conditionscan initiate a non-linear effect in the target zone 114, such ascreating a voxel of destruction in the target zone 114, initiating anacousto-mechanical effect in the target zone 114, initiating anacousto-elastic effect in the target zone 114, or a combination thereof.

For certain applications, a set of parameters for delivering ultrasoundenergy can include an ultrasound frequency ranging from about 1 MHz toabout 10 MHz, an ultrasound power ranging from about 1 kW to about 5 kW,an ultrasound pulse width ranging from about 1 us to about 50 μs, and anultrasound energy ranging from about 1 mJ to about 250 mJ. Deliveringultrasound energy under these conditions can initiate a non-lineareffect in the target zone 114, such as initiating an acousto-mechanicaleffect in the target zone 114. In some aspects, Delivering ultrasoundenergy under these conditions can initiate a non-linear effect and amechanical effect in the target zone 114, such as initiating anacousto-mechanical effect and a cavitation effect in the target zone114.

For certain applications, a set of parameters for delivering ultrasoundenergy can include an ultrasound frequency ranging from about 2 MHz toabout 200 MHz, an ultrasound power ranging from about 1 kW to about 5kW, an ultrasound pulse width ranging from about 500 ps to about 500 ns,and an ultrasound energy ranging from about 500 nJ to about 2.5 mJ. Forcertain applications, the ultrasound frequency can range from about 2MHz to about 5 MHz. Delivering ultrasound energy under these conditionscan initiate a non-linear effect in the target zone 114, such asinitiating an acousto-mechanical effect in the target zone 114,initiating an acousto-elastic effect in the target zone 114, or acombination thereof.

For certain applications, a set of parameters for delivering ultrasoundenergy can include an ultrasound frequency ranging from about 100 kHz toabout 200 MHz, an ultrasound power ranging from about 1 kW to about 50kW, an ultrasound pulse width ranging from about 500 ps to about 750 ns,and an ultrasound pulse width ranging from about 500 nJ to about 37.5mJ. Delivering ultrasound energy under these conditions can initiate anon-linear effect in the target zone 114, such as initiating anacousto-mechanical effect in the target zone 114, initiating anacousto-elastic effect in the target zone 114, or a combination thereof.

For certain applications, a set of parameters for delivering ultrasoundenergy can include an ultrasound frequency ranging from about 2 MHz toabout 10 MHz, an ultrasound power ranging from about 1 kW to about 5 kW,an ultrasound pulse width ranging from about 200 ns to about 1 ms, andan ultrasound energy ranging from about 200 μJ to about 5 J. Deliveringultrasound energy under these conditions can initiate a non-lineareffect, such as an acousto-mechanical effect, in the target zone 114.Delivering ultrasound energy under these conditions can initiate anon-linear effect in the target zone 114, such as creating a voxel ofdestruction in the target zone 114, initiating an acousto-mechanicaleffect in the target zone 114, initiating an acousto-elastic effect inthe target zone 114, or a combination thereof.

In certain aspects, any of the aforementioned sets of parameters caninclude a range disclosed elsewhere in this disclosure that fits withinthe range disclosed in the set of parameters. Depending on the desiredeffect, interleaving pulses can be utilized to alter the temporalparameters or 2 or more pulsed ultrasound energies can be utilized toalter the spatial parameters, the temporal parameters, or both.

In certain aspects, the acousto-mechanical effect or the acousto-elasticeffect generated within an object (for example a targeted tissue) asdescribed herein can be sufficient to overcome Young's Modulus of themedium. Overcoming Young's Modulus can cause the object to fragment,shatter, explode, or any combination thereof. Young's Modulus (E) can becalculated by the following equation:

$\begin{matrix}{E = {\frac{\sigma}{ɛ} = \frac{FL_{0}}{A_{0}\Delta L}}} & (3)\end{matrix}$

where σ is the tensile stress on an object, ε is the extensional strainon an object, F is the force exerted on an object, A₀ is the originalcross-sectional area through which the force is applied, L₀ is theoriginal length of the object, and ΔL is the amount by which the lengthof the object changes.

The ultrasound energy source 102 can be acoustically coupled, directlyor indirectly, to the target zone 114, the ROI 112, the boundary 110, orany combination thereof by way of a coupling agent. In certain aspects,the acoustic coupling agent can be selected from the group consisting ofwater, acoustic coupling gel, other materials providing a desiredtransformation of acoustic impedance from the source to the target, andcombinations thereof.

Referring to FIG. 6, a flow chart is shown of a method 300 for removinga targeted tissue 90 by creating an acousto-mechanical oracousto-elastic effect to fragment a targeted tissue 90, or portionthereof, into sub-particles 146. The sub-particles 146 can be lessvisible in the tissue than the targeted tissue. The sub-particles 146can be of a size which can be up-taken by immune cells and transportedto the lymph system through lymphatic channels 92 for clearance.

Still referring to FIG. 6, the method 300, at process block 302, canbegin with targeting a targeted tissue 90 by, but not limited to, anultrasound imager incorporated in the ultrasound delivery system, bydetermining the depth and size of the targeted tissue 90 within thetissue 80. In certain aspects, the method 300 can include targeting aboundary 110 between the targeted tissue 90 and the tissue 80. Aftertargeting optional steps can be included in the method 300 including,but not limited to, applying a medicant (for example numbing agents orcoupling ultrasound gels) to the skin surface 304 or mechanical effectscan be applied 306.

Still referring to FIG. 6. the method 300, at process block 208, caninclude coupling an ultrasound energy source 102 to the targeted tissue90 and directing a pulsed ultrasound energy 108 from the ultrasoundenergy source 102 into the targeted tissue 90. In certain aspects, themethod 300 can include coupling the ultrasound energy source 102 to aboundary 110 between the targeted tissue 90 and the tissue 80 anddirecting the pulsed ultrasound energy 108 from the ultrasound energysource 102 into the boundary 110 between the targeted tissue 90 and thetissue 80. Directing the pulsed ultrasound energy 108 into the targetedtissue 90 can initiate an acousto-mechanical or acousto-elastic effectin the targeted tissue 90. The pulsed ultrasound energy 108 can haveultrasound properties as disclosed herein. The method 300 can includedelivering a first energy, a second energy, a third energy, or an nthenergy, simultaneously or with various time delays. The first, second,third, or nth energy can be an ultrasound energy or a secondary energy.The method 300 can include delivering a second ultrasound energy intothe targeted tissue 90 prior to the delivery of the pulsed ultrasoundenergy. This second ultrasound energy can create or enhance an acousticmismatch between the target zone or targeted tissue 90 and thesurrounding tissue 80.

At process block 310 the acousto-mechanical or acousto-elastic effectgenerated by the method 300 can overcome a fragmentation threshold,thereby causing fragmentation within the targeted tissue 90 located inthe target zone 114. In certain aspects, the fragmentation can generatesub-particles 146.

At process block 312 sub-particles of a certain size can be up-taken byimmune cells and transported to the lymphatic channel 92 where they arecleared from the tissue. The method 300 can be repeated as indicated byprocess block 314 until a sufficient number of sub-particles of thetargeted tissue are cleared from the tissue to remove the targetedtissue or a portion thereof.

It should be appreciated that the method 300 is “color blind” to thecolor of the targeted tissue, because the ultrasound energy is notabsorbed in a resonant process, such as light absorption.

In certain aspects, the systems and methods described herein can beapplied to systems where the acoustic impedance of the targeted tissue90 and the tissue 80 are different. The acoustic impedance of thetargeted tissue 90 can be at least 10% greater than the acousticimpedance of the tissue 80, including but not limited to, at least 25%greater, at least 50% greater, at least 75% greater, at least 100%greater, at least 200% greater, at least 500% greater, or the acousticimpedance of the targeted tissue 90 can be at least 1000% greater thanthe acoustic impedance of the tissue 80. The acoustic impedance of thetargeted tissue 90 can be less than the acoustic impedance of the tissue80. The acoustic impedance of an object or medium is typically reportedin rayls and can be calculated for any object or medium (Z=ρV, where ρis the density of the object or medium and V is the acoustic velocity inthe object or medium).

In certain aspects, the tissue 80 can have an acoustic impedance between1.3 MRayls and 2.0 MRayls, including but not limited to, an acousticimpedance between 1.5 MRayls and 1.8 MRayls, or an acoustic impedancebetween 1.6 MRayls and 1.7 MRayls.

In certain aspects, the targeted tissue 90 can have an acousticimpedance between 2 MRayls and 10 MRayls, including but not limited toan acoustic impedance between 2 MRayls and 5 MRayls. In certain aspects,the targeted tissue 90 can have an acoustic impedance less than theacoustic impedance of the tissue 80, such as an acoustic impedance ofabout 1.4 MRayls.

The systems and methods described herein can include and/or utilize adatabase of acoustic impedances relating to the various targeted tissues90 and tissues 80 described herein.

The systems and methods described herein can be utilized for thetreatment of cellulite. For example, the acoustic impedance of thefibrous septae, which hold pockets of fat, is greater than the acousticimpedance of the surrounding fat. The acoustic energy can be directed toa boundary between the fibrous septae and the fat to fragment a portionof the fibrous septae. This can result in release of skin above the fat,thereby smoothing the skin above the fat. If the acoustic energy ismisaimed and directed to only the fat, the acoustic energy does notdamage the fat layer, because the acoustic energy was configured toimpact the boundary. Such methods can further include steps to treat thefar, for example, methods described in U.S. Pat. Nos. 8,133,180 and8,663,112, which are hereby incorporated in their entirety by reference.

The control system 104 can be configured to receive a user input, suchas an input that identifies the targeted tissue 90 or the acousticimpedance of the targeted tissue 90. The control system 104 can thenautomatically calculate the acoustic energy necessary to achieve thedesired effect and can be configured to direct the ultrasound energysource 102 to deliver the propagating ultrasound energy 108 having thecalculated properties.

The systems and methods disclosed herein can be useful for medical andnon-medical applications. In one aspect, the systems and methodsdisclosed herein can be useful for acoustic tissue treatment. In oneaspect, the systems and methods disclosed herein can be useful forcosmetic applications, such as the cosmetic enhancement of skin,subcutaneous tissue layers, or a combination thereof. The systems andmethods disclosed herein can be useful for non-invasive and/ornon-surgical applications.

The present invention has been described above with reference to variousexemplary configurations. However, those skilled in the art willrecognize that changes and modifications may be made to the exemplaryconfigurations without departing from the scope of the presentinvention. For example, the various operational steps, as well as thecomponents for carrying out the operational steps, may be implemented inalternate ways depending upon the particular application or inconsideration of any number of cost functions associated with theoperation of the system, e.g., various of the steps may be deleted,modified, or combined with other steps. Further, it should be noted thatwhile the method and system for ultrasound treatment as described aboveis suitable for use by a user proximate the patient, the system can alsobe accessed remotely, i.e., the user can view through a remote displayhaving imaging information transmitted in various manners ofcommunication, such as by satellite/wireless or by wired connectionssuch as IP or digital cable networks and the like, and can direct alocal practitioner as to the suitable placement for the transducer.Moreover, while the various exemplary embodiments may comprisenon-invasive configurations, system can also be configured for at leastsome level of invasive treatment application. These and other changes ormodifications are intended to be included within the scope of thepresent invention, as set forth in the following claims.

1. A non-invasive method of removing a targeted tissue from tissue, thetargeted tissue having an acoustic impedance mismatch with the tissue,the method comprising: a) targeting the targeted tissue; b) coupling anultrasound energy source to the targeted tissue, the ultrasound energysource configured to produce a pulsed first ultrasound energy having afrequency of between 100 kHz and 200 MHz, a pulse duration of between 1ps and 1 ms, and a power between 1 kW and 50 kW; c) initiating anacousto-mechanical or acousto-elastic effect in the targeted tissue bydirecting from 500 nJ to 5 J of the pulsed first ultrasound energy fromthe ultrasound energy source into the targeted tissue.
 2. The method ofclaim 1, wherein the pulse duration is between 1 ns and 10 μs.
 3. Themethod of claim 1, wherein the ultrasound frequency is between 1 MHz and30 MHz.
 4. The method of claim 1, the method further comprising: d)subsequent to step c), directing a second ultrasound energy from theultrasound energy source or a second ultrasound energy source having anultrasound pulse duration of at least 100 μs into the targeted tissue ora portion thereof, thereby initiating a second effect in the targetedtissue or the portion thereof.
 5. The method of claim 4, wherein thesecond effect is a cavitation effect or a thermal effect.
 6. The methodof claim 1, wherein the acousto-mechanical or acousto-elastic effectexceeds a fragmentation threshold of the targeted tissue.
 7. The methodof claim 1, wherein the pulsed first ultrasound energy is a singleultrasound pulse.
 8. The method of claim 1, wherein the tissue issubcutaneous tissue.
 9. The method of claim 1, wherein theacousto-mechanical or acousto-elastic effect moves at least a portion ofthe targeted tissue in the tissue.
 10. The method of claim 9, whereinthe acousto-mechanical or acousto-elastic effect moves at least aportion of the targeted tissue toward a surface of the tissue.
 11. Themethod of claim 10, wherein the acousto-mechanical or acousto-elasticeffect expels at least a portion of the targeted tissue from the tissue.12. The method of claim 9, wherein the acousto-mechanical oracousto-elastic effect moves at least a portion of the targeted tissueaway from a surface of the tissue.
 13. The method of claim 12, whereinthe acousto-mechanical or acousto-elastic effect moves at least aportion of the targeted tissue to a depth where they are no longervisible through the epidermis.
 14. An ultrasound treatment system fortargeted tissue removal comprising: an ultrasound source configured toemit a propagating ultrasound energy having a propagating ultrasoundpulse duration between 100 ps and 1 ms, a propagating ultrasound pulsepower ranging from 1 kW to 50 kW, and a propagating ultrasound frequencybetween 100 kHz and 200 MHz; a control system configured to initiate anacousto-mechanical or acousto-elastic effect within a targeted tissuelocated in a target zone within a medium by directing the ultrasoundenergy source to emit the propagating ultrasound energy to the targetedtissue at an intensity gain between 500 and 25,000, thereby initiatingan acousto-mechanical or acousto-elastic effect within the targetedtissue.
 15. The system of claim 14, wherein the pulse duration isbetween 1 ns and 10 μs.
 16. The system of claim 14, wherein theultrasound frequency is between 1 MHz and 30 MHz.
 17. The system ofclaim 14, the system optionally comprising a second ultrasound source,wherein the ultrasound source or the second ultrasound source isconfigured to emit a second propagating ultrasound energy having asecond propagating ultrasound pulse duration of at least 100 μs, thecontrol system configured to direct the ultrasound energy source or thesecond ultrasound energy source to emit the second propagatingultrasound energy to the target zone.
 18. The system of claim 14,wherein the ultrasound energy source is configured to emit a singleultrasound pulse, the single ultrasound pulse initiating theacousto-mechanical or acousto-elastic effect within the targeted tissue.19-20. (canceled)